title: Optimization and simplification of antiretroviral therapy for adults and children.
abstract: OBJECTIVE
  The review reflects on opportunities and challenges for HIV treatment optimization for the next 5 years.
  
  
  RESULTS
  Considering all currently available options, the fixed-dose combination of tenofovir + lamivudine (or emtricitabine) + efavirenz is considered as the best option for first-line treatment for the short to medium term. Second-line therapy will likely continue to be comprised of a boosted protease inhibitor in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), with potential for combining with integrase inhibitors. For children, there is potential for simplification and harmonization with adult antiretroviral regimens. First-line therapy for children younger than 3 years of age may be best delivered using two nucleoside reverse transcriptase inhibitors (NRTIs) and a boosted protease inhibitor; above 3 years of age, the standard of care is two NRTIs and a non-nucleoside reverse transcriptase inhibitor (NNRTI) as recommended for adults. Important research questions include the dosing and safety of new antiretroviral agents and formulations, particularly once-daily fixed-dose combinations, the role of integrase inhibitors and the optimal second-line regimen for NNRTI-exposed children who fail protease inhibitor-containing first-line regimens.
  
  
  CONCLUSIONS
  Treatment simplification is critical to further antiretroviral therapy scaling-up and support long-term retention in care. Future guidance should consider the broader benefits of earlier antiretroviral therapy initiation beyond potential AIDS mortality reduction, notably mitigation of short- and long-term HIV-associated comorbidities, reduction of HIV transmission, increased retention in care, and enhancing programme simplification.
authors.affiliation: aHIV/AIDS Department, World Health Organization, Geneva, Switzerland bDepartments of Medicine, Pharmacology, and International Health, Johns Hopkins University, Baltimore, Maryland, USA cDepartment of Pharmacological Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy dClinton Health Access Initiative, Boston, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
authors.forename: Charles
authors.initials: C
authors.lastname: Flexner
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.forename: David
authors.initials: D
authors.lastname: Ripin
authors.forename: Marco
authors.initials: M
authors.lastname: Vitoria
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D002648:Child; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D055118:Medication Adherence; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents